Asthma is a heterogeneous inflammatory disease of the airways that clinically manifests with symptoms and signs of airflow obstruction of varied severity. Although the majority of asthma patients can be effectively treated with currently available medications, such as inhaled glucocorticoids and bronchodilators, a substantial subset exists who remain difficult-to-treat and manifest with severe disease. These patients account for a relatively large proportion of resource expenditure (Chung et al. 2014).
While asthma has been considered to be driven by T helper cell type 2 (Th2) cells, such as IgE activated mast cells, eosinophils and their products, data suggest that a Th2-high gene signature is present in the airways of only 50% of asthmatics (Woodruff et al. 2009). Non-eosinophilic airway inflammation occurs in approximately 50% of patients with asthma, of which a significant proportion include moderate and severe asthmatics (Thomson 2016). Non-Th2-high or non-eosinophilic inflammation is associated with an impaired therapeutic response to inhaled corticosteroids (McGrath et al. 2012), and hence asthmatics with non-allergic and non-eosinophilic phenotype are not eligible for biologic therapies with anti-IgE and anti-IL5 antibodies. Thus, a large unmet medical need exists in moderate and severe non-allergic non-eosinophilic asthmatics who suffer from symptoms of poorly controlled asthma, such as cough and shortness of breath, despite being compliant on therapy with inhaled glucocorticoids and bronchodilators.